{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:52:18Z","timestamp":1771908738582,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biometrics"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The presence of protein aggregates in cells is a known feature of many human age\u2010related diseases, such as Huntington's disease. Simulations using fixed parameter values in a model of the dynamic evolution of expanded polyglutaime (PolyQ) proteins in cells have been used to gain a better understanding of the biological system. However, there is considerable uncertainty about the values of some of the parameters governing the system. Currently, appropriate values are chosen by ad hoc attempts to tune the parameters so that the model output matches experimental data. The problem is further complicated by the fact that the data only offer a partial insight into the underlying biological process: the data consist only of the proportions of cell death and of cells with inclusion bodies at a few time points, corrupted by measurement\u00a0error. Developing inference procedures to estimate the model parameters in this scenario is a significant task. The model probabilities corresponding to the observed proportions cannot be evaluated exactly, and so they are estimated within the inference algorithm by repeatedly simulating realizations from the model. In general such an approach is computationally very expensive, and we therefore construct Gaussian process emulators for the key quantities and reformulate our algorithm around these fast stochastic approximations. We conclude by highlighting appropriate values of the model parameters leading to new insights into the underlying biological\u00a0processes.<\/jats:p>","DOI":"10.1111\/biom.13467","type":"journal-article","created":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T05:50:39Z","timestamp":1618033839000},"page":"1195-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Parameter inference for a stochastic kinetic model of expanded polyglutamine proteins"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-9140","authenticated-orcid":false,"given":"H. F.","family":"Fisher","sequence":"first","affiliation":[{"name":"School of Mathematics, Statistics &amp; Physics Newcastle University Newcastle Upon Tyne UK"},{"name":"Population Health Sciences Institute Newcastle University Newcastle Upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. J.","family":"Boys","sequence":"additional","affiliation":[{"name":"School of Mathematics, Statistics &amp; Physics Newcastle University Newcastle Upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-0275","authenticated-orcid":false,"given":"C. S.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"School of Mathematics, Statistics &amp; Physics Newcastle University Newcastle Upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. J.","family":"Proctor","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle Upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-1279","authenticated-orcid":false,"given":"A.","family":"Golightly","sequence":"additional","affiliation":[{"name":"School of Mathematics, Statistics &amp; Physics Newcastle University Newcastle Upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.780654"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02998"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1198\/TECH.2009.08019"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1198\/004017007000000092"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11222-007-9043-x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2159468"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v076.i01"},{"key":"e_1_2_11_9_1","first-page":"241","volume-title":"The Oxford Handbook of Applied Bayesian Analysis","author":"Cumming J.A.","year":"2010"},{"key":"e_1_2_11_10_1","volume-title":"shinystan: Interactive Visual and Numerical Diagnostics and Posterior Analysis for Bayesian Models","author":"Gabry J.","year":"2018"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0237-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177011136"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11222-016-9667-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100540a008"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.481811"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1378322"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2007.00587.x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2011.0047"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1198\/jasa.2009.0005"},{"key":"e_1_2_11_20_1","first-page":"155","volume-title":"The Oxford Handbook of Applied Bayesian Analysis","author":"Henderson D.A.","year":"2010"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1009212673"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7160934"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11222-013-9440-2"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-4-92"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012857"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.025"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13413"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3758(94)00035-T"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ress.2005.11.025"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0018"},{"key":"e_1_2_11_31_1","volume-title":"Gaussian Processes for Machine Learning","author":"Rasmussen C.E.","year":"2006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1066"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-3799-8"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2013.09.012"},{"key":"e_1_2_11_35_1","unstructured":"Stan Development Team(2018)RStan: the R interface to Stan. R package version 2.18.2."},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000944"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2008.0172"},{"key":"e_1_2_11_38_1","volume-title":"Stochastic Processes in Physics and Chemistry","author":"Kampen N.G.","year":"2001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1214\/12-STS412"},{"key":"e_1_2_11_40_1","volume-title":"Stochastic Modelling for Systems Biology","author":"Wilkinson D.J.","year":"2018"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-S12-S3"}],"container-title":["Biometrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/biom.13467","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/biom.13467","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/biom.13467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T18:12:17Z","timestamp":1706292737000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biometrics\/article\/78\/3\/1195-1208\/7477185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/biom.13467"],"URL":"https:\/\/doi.org\/10.1111\/biom.13467","archive":["Portico"],"relation":{},"ISSN":["0006-341X","1541-0420"],"issn-type":[{"value":"0006-341X","type":"print"},{"value":"1541-0420","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"2019-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}